Isoxazoles and Isoxazolines by 1,3‐Dipolar Cycloaddition: Base‐Catalysed Condensation of Primary Nitro Compounds with Dipolarophiles

Abstract

1,4-Diazabicyclo[2.2.2]octane (DABCO) or other suitable Nbases cause primary activated nitro compounds to condense with alkenes to yield isoxazolines or with alkynes to give isoxazoles. As the molar ratio of the base with respect to the dipolarophile decreased, the reaction became slower, but the nitro compound became more resistant to hydrolytic cleavage. The best results were achieved with a molar ratio of base in the range of 0.05-0.1. The reactions were carried out in chloroform at 60°C; for ethyl nitroacetate and phenylnitromethane, ethanol at 80°C can be employed with better

Synthesis of 3,5-Disubstituted Isoxazoles and Isoxazolines in Deep Eutectic Solvents

“…The second one is the 1,3-dipolar cycloaddition reaction between alkynes or alkenes with nitrile oxides, generated in situ from aldoximes or nitroalkanes. [12][13][14][15][16][17][18][19][20][21][22][23] In turn, these heterocycles can be transformed into β-functionalizes carbonylic compounds, 24 by cleavage of the labile N-O heterocyclic bond.…”

Acid–Base‐Catalysed Condensation Reaction in Water: Isoxazolines and Isoxazoles from Nitroacetates and Dipolarophiles

“…Reaction in water/reaction on water: As reported in our previous papers, [27,28] ethyl nitroacetate reacts with various dipolarophiles under base catalysis to afford 3-ethoxycarbonylisoxazolines by a cycloaddition-condensation reaction process. To date, these reactions have been conveniently and successfully carried out in chloroform.…”

“…The spectral data are identical to those previously reported. [28] Condensation reaction of ethyl nitroacetate with 10-undecen-1-ol to give ethyl 5-(2-hydroxynonyl)-4,5-dihydro-3-isoxazolecarboxylate (7 a): The reaction of 10-undecen-1-ol (72 mg, 0.423 mmol) with 1 a after 72 h gave unreacted alcohol (12 mg, R f = 0.64) and 7 a (93 mg, 93 % calculated taking into account recovered 10-undecen-1-ol) after chromatography (petroleum ether/ethyl acetate 4:1, then petroleum ether/ethyl acetate 3:1) as a white solid. R f = 0.18; m.p.…”

Nitroalkanes as key building blocks for the synthesis of heterocyclic derivatives

“…58 Reaction of the nitro compounds 5 with alkenes leads regioselectively to the isoxazoline 152, while the same process with alkynes produces isoxazoles, 153. In the proposed catalytic cycle the hydrogen-bonded ion pair formed between the nitronate and the protonated base in chloroform undergoes reversible cycloaddition with the dipolarophile, and then the hydrogen-bonded intermediate adduct releases water by reaction with a second nitro-molecule to give the product and the hydrogen-bonded nitronate.…”